Association Between Depressive Symptoms and Insulin Resistance and the Impact of the Menopausal Transition

Context:Recent meta-analyses and cross-sectional studies propose that insulin resistance (IR) is not a lasting feature of depression. However, longitudinal evidence is lacking, particularly in midlife women across menopause and ethnically diverse cohorts. Objective: To assess the longitudinal association between depressive symptoms and IR among midlife women and determine if this association varies by menopausal status and ethnicity. Methods:The study population comprised 2,829 White, Black, Hispanic, Chinese, and Japanese women from the Study of Women’s Health Across the Nation followed for approximately 20 years. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression (CES-D) scale, and IR was obtained from the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Linear mixed-effects modeling was used to estimate the association between depressive symptoms (CES-D score ≥16, indicating risk for clinical depression) and HOMA-IR, adjusting for important confounders. Results:In multivariable analyses simultaneously including current depressive symptoms and depressive symptoms from the prior visit in the model, the estimated effect of current CES-D score ≥16, but not prior CES-D score ≥16, was statistically significantly associated with higher log-HOMA-IR levels (β = 0.03, 95% confidence interval [CI]: 0.01, 0.06). The relationship between current depressive symptoms and IR was strongest among Hispanic women (interaction p = 0.005; β = 0.18, 95% CI: 0.08, 0.27). Conclusion:Current reporting of CES-D score ≥16, but not prior reporting, was associated with elevated IR over time among midlife women. This study provides longitudinal evidence in support of IR as a temporary feature of depression. Moreover, the results suggest that Hispanic women with higher depressive symptoms may be particularly susceptible to IR.